The cognitive improvement induced by cordycepin in AD model and the underlying mechanisms were studied in the present study.Intraperitoneal injection of D-galactose combined with microinjection of Aβ_25-35 in hippocampus were used to establish the AD model.The cognitive ability was evaluated by Y maze test,and the potential mechanisms were determined by the enzymatic activity of AChE and the neuronal morphology analysis respectively.Our results showed that the cognitive ability of AD rats was significantly impaired when compared with control group,as well as the AChE activity increased significantly and neurons damaged seriously.Interestingly,we found that the cognitive ability was obviously improved,AChE activity was significantly decreased and neuronal damaged was improved in cordycepin treated group when compared with the AD model rats.Moreover,there is no significant difference of the results between cordycepin treated group and control group.These results indicate that cordycepin can ameliorate cognitive impairments induced by Aβ combined with D-galactose,and the potential mechanism may be related to enhancing the function of cholinergic nervous system and reducing the damage of hippocampal neurons.